Asymmetry metrology is performed using at least a portion of Mueller matrix elements, including, e.g., the off-diagonal elements of the Mueller matrix. The Mueller matrix may be generated using, e.g., a spectroscopic or angle resolved ellipsometer that may include a rotating compensator. The Mueller matrix is analyzed by fitting at least a portion of the elements to Mueller matrix elements calculated using a rigorous electromagnetic model of the sample or by fitting the off-diagonal elements to a calibrated linear response. The use of the Mueller matrix elements in the asymmetry measurement permits, e.g., overlay analysis using in-chip devices thereby avoiding the need for special off-chip targets.